Porphyromonas gingivalis (W83) Infection Induces Alzheimer's Disease-Like Pathophysiology in Obese and Diabetic Mice.

BACKGROUND: Periodontal disease(s) and metabolic illnesses negatively impact the quality of life and, eventually mental health. OBJECTIVE: This study investigated the effect of Porphyromonas gingivalis (W83) oral infection on the development of Alzheimer's disease (AD) pathophysiology in a wild-type obese, diabetic (db/db) mouse model. METHODS: The db/db mice were either orally infected with P. gingivalis and Fusobacterium nucleatum or sham infected for 16 weeks. The presence of amyloid-ß (Aß) and neurofibrillary tangles (NFTs) were assessed using a silver impregnation technique and subsequently by immunohistochemistry for tau and neuroinflammation. The mRNA abundance of a panel of 184 genes was performed using quantitative real-time PCR, and the differentially expressed genes were analyzed by Ingenuity Pathway Analysis. RESULTS: While no Aß plaques and NFTs were evident by silver impregnation, immunohistochemistry (glial cell markers) of the P. gingivalis-infected mice tissue sections exhibited neuroinflammation in the form of reactive microglia and astrocytes. Anti-tau immunopositivity, in addition to cells, was prominent in thickened axons of hippocampal CA neurons. The mRNA abundance of crucial genes in the insulin signaling pathway (INSR, IGF1, IRS, IDE, PIK3R, SGK1, GYS, GSK3B, AKT1) were upregulated, potentially exacerbating insulin resistance in the brain by P. gingivalis oral infection. Increased mRNA abundance of several kinases, membrane receptors, transcription factors, and pro-inflammatory mediators indicated hyperactivation of intracellular cascades with potential for tau phosphorylation and Aß release in the same infection group. CONCLUSION: P. gingivalis W83 infection of db/db mice provides a disease co-morbidity model with the potential to reproduce AD pathophysiology with induced periodontal disease.

Low Intakes of Iodine and Selenium Amongst Vegan and Vegetarian Women Highlight a Potential Nutritional Vulnerability.

Vegan and vegetarian diets are becoming increasingly popular in the UK. Due to the avoidance of animal products there can be significant differences in nutrient intakes between meat-eaters and vegetarians, and especially vegans. Importantly, research has identified that both vegans and vegetarians may be vulnerable to low intakes of some micronutrients. The aim of this study was to investigate micronutrient intake in omnivorous, vegetarian and vegan women. In total, 62 women (26 omnivores, 16 vegetarians, 20 vegans, mean age 31.6 ± 12.4 y, mean BMI 24.1 ± 1.6 kg/m 2 ) completed 4-day diet diaries. Diet intake data was analyzed using Nutritics and nutrient intake levels were compared with national dietary recommendations (RNIs). Statistical analysis was performed using SPSS, with differences between the groups identified using ANOVA with post-hoc Bonferroni correction. All groups recorded intakes of vitamin D, iron, iodine and selenium below RNI. The vegan group had significantly lower intakes of vitamin D, vitamin B12, calcium, selenium and iodine than vegetarians and omnivores (p < 0.05), with particularly low intakes of selenium (24.7 ± 11.9 µg) and iodine (24.4 ± 12.7 µg). These results suggest that adult women in the UK are at risk of low intakes of several vitamins and minerals, with the exclusion of animal products conferring an additional vulnerability, particularly with respect to selenium and iodine, both of which play important roles in thyroid hormone production. This study highlights iodine and selenium intakes to be a concern amongst women who follow vegan diets, and the necessity of further research to identify if low intake translates to biochemical markers and functional status.

Are there functional consequences of a reduction in selenium intake in UK subjects?

Dietary Se levels in the UK have fallen over the last 20 years and recent surveys indicate that average Se intakes are 30-40 microg/d, which is well below the current UK reference nutrient intake for adult men (75 microg/d) or women (60 microg/d). Functional consequences of this decline have not been recognised, although epidemiological data suggest it may contribute to increased risk of infections and incidence of some cancers. Previous data have indicated that biochemical changes in Se-dependent proteins occur in otherwise healthy UK subjects given small Se supplements. The current studies have focused on the effect of small Se supplements on the immune response since there is evidence of specific interactions between Se intake and viral replication, and since the potential anti-cancer effects of Se may be mediated by non-antioxidant effects of Se such as changes in immune function. Data indicate that subjects given small Se supplements (50 or 100 microg Se/d) have changes in the activity of Se-dependent enzymes and evidence of improved immune function and clearance of an administered live attenuated virus in the form of poliovirus vaccine. Responses of individual subjects to Se supplements are variable, and current work is evaluating potential explanations for this variability, including genetic variability and pre-existing Se status.

Antioxidant properties of aged garlic extract: an in vitro study incorporating human low density lipoprotein.

Oxidation of low-density lipoprotein (LDL) has been recognized as playing an important role in the development and progression of atherosclerotic heart disease. Human LDL was isolated and challenged with a range of oxidants either in the presence or absence of AGE or its diethyl ether extract. Oxidative modification of the LDL fraction using CuSO(4), 5-lipoxygenase and xanthine/xanthine oxidase was monitored by both the appearance of thiobarbituric-acid substances (TBA-RS) and an increase in electrophoretic mobility. This study indicates that AGE is an effective antioxidant as it scavenged superoxide ions and reduced lipid peroxide formation in cell free assays. Superoxide production was completely inhibited in the presence of a 10% (v/v) aqueous preparation of AGE and reduced by 34% in the presence of a 10% (v/v) diethyl ether extract of AGE. The presence of 10% (v/v) diethyl ether extract of AGE significantly reduced Cu(2+) and 15-lipoxygenase-mediated lipid peroxidation of isolated LDL by 81% and 37%, respectively. In addition, it was found that AGE also had the capacity to chelate copper ions. In contrast, the diethyl ether extract of AGE displayed no copper binding capacity, but demonstrated distinct antioxidant properties. These results support the view that AGE inhibits the in vitro oxidation of isolated LDL by scavenging superoxide and inhibiting the formation of lipid peroxides. AGE was also shown to reduce LDL oxidation by the chelation of Cu(2+). Thus, AGE may have a role to play in preventing the development and progression of atherosclerotic disease.

Dietary supplementation with aged garlic extract reduces plasma and urine concentrations of 8-iso-prostaglandin F(2 alpha) in smoking and nonsmoking men and women.

F(2)-isoprostanes are recently described prostaglandin F isomers produced by cyclooxygenase-independent free radical peroxidation of arachidonic acid. Their quantification in plasma and urine is a sensitive and specific indicator of lipid peroxidation and, hence, of oxidative stress in vivo. Some components of garlic are known to possess antioxidant properties. Thus, we have investigated the effect of dietary supplementation with aged garlic extract (AGE; Kyolic; Wakunaga of America, Mission Viejo, CA) on the plasma and urine concentrations of the F(2)-isoprostane 8-iso-prostaglandin F(2 alpha) (8-iso-PGF(2 alpha)). Because smokers are exposed to increased oxidative stress, this study was performed in both smoking and nonsmoking subjects. Plasma and urine concentrations of 8-iso-PGF(2 alpha) in nonsmoking individuals were 1.25 +/- 0.19 nmol/L and 272 +/- 53 pmol/mmol of creatinine, respectively. In age- and sex-matched smokers, plasma and urine concentrations of 8-iso-PGF(2 alpha) were 58% and 85% higher, respectively. Dietary supplementation with AGE for 14 d reduced plasma and urine concentrations of 8-iso-PGF(2 alpha) by 29% and 37% in nonsmokers and by 35% and 48% in smokers. Fourteen days after cessation of dietary supplementation, plasma and urine concentrations of 8-iso-PGF(2 alpha) returned to values not different from those before ingestion of AGE in both groups. Thus, dietary supplementation with AGE may be useful in reducing oxidative stress in humans.